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Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy

Lookup NU author(s): Dr Naomi Warren, Dr Margaret Piggott, Liz Greally, Professor David Burn

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Abstract

Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic α4β2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n = 15) and controls (n = 32). In PSP, there was a marked loss of dopamine transporter and nicotinic α4β2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors. © 2007 Movement Disorder Society.


Publication metadata

Author(s): Warren NM, Piggott MA, Greally E, Lake M, Lees AJ, Burn DJ

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2007

Volume: 22

Issue: 11

Pages: 1594-1600

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/mds.21573

DOI: 10.1002/mds.21573

PubMed id: 17534953


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Funding

Funder referenceFunder name
G0400074Medical Research Council
G0502157Medical Research Council

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